Specific binding of haptoglobin to human neutrophils and its functional consequences.
Haptoglobin, an acute phase reactant protein, has been shown to modulate various facets of immune responses. In this paper we examined the effect of haptoglobin on human neutrophils at the molecular level. First, we found that native haptoglobin binds at two distinct sites on neutrophils. We then examined the effects of this binding at normal and pathophysiological concentrations of haptoglobin found in human serum. Of the various functional parameters assessed, neutrophil respiratory burst activity, as assessed by superoxide (O2-) production, was inhibited by native haptoglobin when the cells were stimulated with formylmethionyl-leucylphenylalanine (FMLP), arachidonic acid (AA), and opsonized zymosan. The rise in intracellular calcium induced by FMLP stimulation was also inhibited by native haptoglobin. Since the generation of O2- was unaffected by native haptoglobin in phorbol myristate acetate (PMA)-stimulated neutrophils, the likely site of haptoglobin inhibition on neutrophil function is at a point of receptor-ligand interaction in the activation cascade. The role of haptoglobin as a modifier of the immune response has here been extended to altered neutrophil function stimulated by diverse agonists.
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S K
SK
Department of Microbiology, Boston University School of Medicine, MA 02118.
Pavlotsky
N
N
Tauber
A I
AI
D002118:Calcium / Q000378:metabolism; D003208:Concanavalin A / Q000378:metabolism; D006242:Haptoglobins / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007107:Immune System / Q000502:physiology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism* / Q000502:physiology; D010087:Oxides / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology
D006242:Haptoglobins; D010087:Oxides; D003208:Concanavalin A; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002118:Calcium